A number of biopharmaceuticals are formulated and provided ready for clinical administration without further manipulation, however, many products require varying degrees of handling by the nurse, pharmacist, or physician. During handling and administration, physical and chemical stability of the protein must be maintained. Loss of stability can occur when the protein formulation is diluted to low concentrations with intravenous (i.v.) solutions, thus lowering the excipient concentration and modifying the composition and properties of the original drug product formulation. When delivering a biopharmaceutical product via the i.v. route several factors must be considered including protein properties, formulation composition, concentration of the active product to be delivered, choice of diluent, contact surfaces, and infusion time and rate. The contact surface is of particular interest as proteins tend to absorb at interfaces due to their amphiphilic nature. With the widespread use of a variety of plastic polymers in syringes and i.v. infusion containers and lines, the risk of protein loss by adsorption is significant, especially at low concentrations (<0.5 mg/mL). Thus, protein loss due to adsorption onto filters, containers, syringes, and tubing must be investigated and addressed during drug product development, particularly for low dose products.
The present invention provides formulations suitable for low concentration therapeutic proteins.